Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH)

Background: Gut microbiota may play a role in non-alcoholic steatohepatitis (NASH). Previous studies showed that prebiotics and probiotics might halt the progression of steatohepatitis. Aim: To clarify the potential effect of Synbiotic 2000®Forte (Synb) in preventing or ameliorating diet induced ste...

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Main Authors: Helena Cortez-Pinto, Paula Borralho, Jorge Machado, Maria T. Lopes, Inês V. Gato, António M. Santos, António S. Guerreiro
Format: Article
Language:English
Published: Karger Publishers 2016-05-01
Series:GE: Portuguese Journal of Gastroenterology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2341454516000132
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author Helena Cortez-Pinto
Paula Borralho
Jorge Machado
Maria T. Lopes
Inês V. Gato
António M. Santos
António S. Guerreiro
author_facet Helena Cortez-Pinto
Paula Borralho
Jorge Machado
Maria T. Lopes
Inês V. Gato
António M. Santos
António S. Guerreiro
author_sort Helena Cortez-Pinto
collection DOAJ
description Background: Gut microbiota may play a role in non-alcoholic steatohepatitis (NASH). Previous studies showed that prebiotics and probiotics might halt the progression of steatohepatitis. Aim: To clarify the potential effect of Synbiotic 2000®Forte (Synb) in preventing or ameliorating diet induced steatohepatitis, particularly in fibrosis progression and how this intervention correlates with gut microbiota composition and endotoxinemia. Methods: Twenty-seven C57BL/6 mice were divided into three groups: chow diet (CD, n = 7); high-fat choline deficient diet (HFCD, n = 10) and HFCD diet supplemented with Synbiotic 2000®Forte (four probiotic strains and four prebiotics mixture) (HFCD + Synb, n = 10). At 6 and 18 weeks, blood samples (lipopolysaccharides assay – LPS), cecal feaces (gut microbiota) and liver tissue (histology) were collected for analysis. Results: Both HCFD diet mice developed steatohepatitis with ballooning at 6 and 18 weeks, opposite to CD. Comparison of histological scores in HFCD and HFCD + Synb, at 6 and 18 weeks showed no significant difference regarding steatosis, inflammation, or ballooning. Evaluating fibrosis with Sirius Red, and degree of smooth-muscle cell activation, HFCD mice had significantly more fibrosis; addition of Synb significantly reduced fibrosis at 6 weeks and 18 weeks. Serum endotoxin levels were similarly increased in HFCD and HFCD + Synb at week 6; however at week 18 HFCD + Synb had significantly lower endotoxin levels than HFCD. Gut microbiota of HFCD vs CD, showed no significant differences regarding the phyla Firmicutes and Bacteroidetes, either at 6 or 18 weeks; Proteobacteria increased at 6 week (3.3) and 18 week (7.5), while the addition of Synb resulted in a decrease at week 18 (−3.90). Fusobacteria markedly increase at week 18 (10.0), but less so with the addition of Synb (5.2). Conclusion: Synbiotic 2000®Forte is able to modulate the mouse gut microbiota reducing the degree of fibrosis while simultaneously decreasing endotoxemia.
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spelling doaj.art-92bb50393e2d4a3181f9a91ffb4186f92022-12-21T19:51:34ZengKarger PublishersGE: Portuguese Journal of Gastroenterology2341-45452016-05-0123313214110.1016/j.jpge.2016.01.004Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH)Helena Cortez-Pinto0Paula Borralho1Jorge Machado2Maria T. Lopes3Inês V. Gato4António M. Santos5António S. Guerreiro6Gastroenterology and Hepatology Department, Centro Hospitalar Lisboa Norte, Lisbon, PortugalPathology Institut, Faculdade de Medicina de Lisboa, Lisbon, PortugalInfectious Diseases Department, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, PortugalCEDOC – Chronic Diseases Research Center, NOVA Medical School, Faculdade de Ciências Médicas de Lisboa, Lisbon, PortugalInfectious Diseases Department, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, PortugalCEDOC – Chronic Diseases Research Center, NOVA Medical School, Faculdade de Ciências Médicas de Lisboa, Lisbon, PortugalCEDOC – Chronic Diseases Research Center, NOVA Medical School, Faculdade de Ciências Médicas de Lisboa, Lisbon, PortugalBackground: Gut microbiota may play a role in non-alcoholic steatohepatitis (NASH). Previous studies showed that prebiotics and probiotics might halt the progression of steatohepatitis. Aim: To clarify the potential effect of Synbiotic 2000®Forte (Synb) in preventing or ameliorating diet induced steatohepatitis, particularly in fibrosis progression and how this intervention correlates with gut microbiota composition and endotoxinemia. Methods: Twenty-seven C57BL/6 mice were divided into three groups: chow diet (CD, n = 7); high-fat choline deficient diet (HFCD, n = 10) and HFCD diet supplemented with Synbiotic 2000®Forte (four probiotic strains and four prebiotics mixture) (HFCD + Synb, n = 10). At 6 and 18 weeks, blood samples (lipopolysaccharides assay – LPS), cecal feaces (gut microbiota) and liver tissue (histology) were collected for analysis. Results: Both HCFD diet mice developed steatohepatitis with ballooning at 6 and 18 weeks, opposite to CD. Comparison of histological scores in HFCD and HFCD + Synb, at 6 and 18 weeks showed no significant difference regarding steatosis, inflammation, or ballooning. Evaluating fibrosis with Sirius Red, and degree of smooth-muscle cell activation, HFCD mice had significantly more fibrosis; addition of Synb significantly reduced fibrosis at 6 weeks and 18 weeks. Serum endotoxin levels were similarly increased in HFCD and HFCD + Synb at week 6; however at week 18 HFCD + Synb had significantly lower endotoxin levels than HFCD. Gut microbiota of HFCD vs CD, showed no significant differences regarding the phyla Firmicutes and Bacteroidetes, either at 6 or 18 weeks; Proteobacteria increased at 6 week (3.3) and 18 week (7.5), while the addition of Synb resulted in a decrease at week 18 (−3.90). Fusobacteria markedly increase at week 18 (10.0), but less so with the addition of Synb (5.2). Conclusion: Synbiotic 2000®Forte is able to modulate the mouse gut microbiota reducing the degree of fibrosis while simultaneously decreasing endotoxemia.http://www.sciencedirect.com/science/article/pii/S2341454516000132MicrobiotaMiceNon-alcoholic Fatty Liver DiseasePrebioticsProbiotics
spellingShingle Helena Cortez-Pinto
Paula Borralho
Jorge Machado
Maria T. Lopes
Inês V. Gato
António M. Santos
António S. Guerreiro
Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH)
GE: Portuguese Journal of Gastroenterology
Microbiota
Mice
Non-alcoholic Fatty Liver Disease
Prebiotics
Probiotics
title Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH)
title_full Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH)
title_fullStr Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH)
title_full_unstemmed Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH)
title_short Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH)
title_sort microbiota modulation with synbiotic decreases liver fibrosis in a high fat choline deficient diet mice model of non alcoholic steatohepatitis nash
topic Microbiota
Mice
Non-alcoholic Fatty Liver Disease
Prebiotics
Probiotics
url http://www.sciencedirect.com/science/article/pii/S2341454516000132
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